1. STEROID EFFECTS ON SDN-POA The sexually dimophic nucleus of the preoptic area (SDN-POA) of rat is larger in male than in female. Perinatal treatments of females with T or DES (E2 analogue) induce an increase of the volume of SDN in females

2. Influences of the perinatal hormonal environment on the volume of the SDN-POA TP D-4: females with single injection of 1.25mg testosterone propionate on day 4 PROL TP: females with daily injections of TP for a prolonged period (till day 10) EB-D2: females with single injection of 100 µg estradiol benzoate on day 2 PROL DES: females with daily injections of EB for a prolonged period (till day 10) GX D-1: gonadectomized males on day 1 TP D-2: gonadectomized males on day 1 + single injection of 100µg TP on day 2 TFM: males with testicular feminizing mutation

3. O: adul rats pre- (16 day) and postnatally (for 10 days after birth) treated with sesame oil CA: adul rats pre- and postnatally treated with cyproterone acetate (androgen antagonist) TA: adul rats pre- and postnatally treated with tamoxifen (estrogen antagonist) Sacrifice: 2 months Endocrine effects - Cyproterone induces a cyclic release of gonadotropins in male - Tamoxifen induces anovulation in female Tamoxifen reduces the volume of SDN only in male DEVELOPMENT AND DIFFERENTIATION OF THE SDN ARE UNDER CONTROL OF ESTROGENS (Dohler et al, Neuroendocrinol, 1986)

4. Sexual Differentiation of the Brain n The undifferentiated brain is basically female: the default structure n Perinatal testosterone transforms it into the male structure via estradiol n The transformation is governed by aromatase (T  E) which is limiting the production of E2 n Alpha-fetoprotein prevents masculinization of females Undifferentiated brain Masculine brain Female brain Perinatal testosterone Estradiol aromatase

5. CLASSIC MODEL Masculinization of the circuits dipends by gonadal hormone exposition Female circuits develop in absence of hormones

6. Behavioral Sexual Differentiation “Masculinization” +/- = display mounts Pink = normal female White = normal male Black = female treated with perinatal androgen Yellow = male castrated on PN1 ♀ ♂ ♂ ♀ +T n Beach et al. (rats): +/- + + -

7. TESTOSTERONE ROLE IN MALE In male rodents T secreted by testes enters into the brain and it is aromatized in E2. E2 binds estrogen receptors and controls genic expression in order to masculinize and defeminize the nervous circuits controlling the sexual behavior. The real motor of the masculine differentiation of the brain is the locally produced estradiol

8. …… following ………. n The testosterone and its metabolites are active during a specific period (critical period) and they induce the differentiation of both brain and behavior. Organizational effect n Irreversible changes of the sexual behavior n Irreversible changes in some nervous circuits

10. CONCLUSIONS n In the preoptic area there is a nerve network that regulates influence of steroids on male reproductive functions n The central part of the circuit is the medial preoptic nucleus (MPN), that inside contains the sexually dimorphic nucleus (SDN) n The circuit is interposed between the sensitive and the motor components Lesions of the preoptic area may induce a significative decrease of male sexual behavior